Pentoxifylline Add-on Therapy for Schizophrenia

Phase 1

• Conditions: Schizophrenia
• Interventions: Drug: Oxopurin

• Registration Number: NCT05073640
• Lead Sponsor: Mazra Mental Health Center

Brief Summary

The etiology and pathogenesis of schizophrenia remain unclear. The immune dysfunction hypothesis for schizophrenia has attracted increasing attention from researchers, and substantial evidence suggested that the levels of TNF-α and other cytokines are markedly elevated in patients with schizophrenia. The investigators aim to evaluate the adjuvant therapeutic effect of Pentoxifylline, a TNF-α inhibitor that crosses the blood-brain barrier, in a randomized, double-blind, 6-week trial. Individuals with schizophrenia will receive either Pentoxifylline or a matching placebo as an add-on treatment to antipsychotic agents. Subjects' positive and negative symptoms and plasma concentration of neuroinflammatory markers will be monitored at baseline and every two weeks until the end of the trial.

Detailed Description

Ninety schizophrenic patients will be randomized to a Pentoxifylline (400 mg twice a day) or placebo treatment for six weeks. Pentoxifylline and placebo will be added to the current antipsychotic drug treatment. Participants will be asked to fill a socio-demographic questionnaire and to undergo a clinical differential diagnosis using the Symptoms Check List (SCL)-90, Clinical Global Impression (CGI), positive and negative symptoms scale (PANSS), and Hamilton depression rating scale (HAM-D). Following baseline evaluation, participants will be monitored for symptoms every two weeks until the end of the trial (overall three visits) using CGI, PANSS, and HAM-D. Adverse effects will be documented every visit using the Treatment Emergent Symptom Scale. Finally, yet importantly, a blood sample will be collected at baseline and every two weeks until the end of the trial to study the treatment effect on inflammatory markers.

Study Timeline

• Study Start: 2019-04-20
• Status Verified: 2021-09
• Study First Submitted: 2021-09-29
• Study First Submitted QC: 2021-09-29
• Last Update Submitted: 2021-09-29
• Study First Posted: 2021-10-11
• Last Update Posted: 2021-10-11
• Primary Completion: 2022-04
• Study Completion: 2022-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 90

Inclusion Criteria

1. Patients meeting the DSM-V criteria for schizophrenia spectrum disorders.
2. Clinical Global Impression (CGI) score ≥ 4 and ≤ 6 at screening.
3. Initiated treatment with a stable dosage of typical and/or atypical antipsychotic medication for at least four weeks.

Exclusion Criteria

1. Previous sensitivity to pentoxifylline (PTF).
2. Chronic immune and/or inflammatory diseases (such as rheumatoid arthritis, systemic lupus erythematosus, chronic inflammatory bowel disease).
3. Consumption for > 3 consecutive days of any immune-modulating or anti-inflammatory drug in the last month.
4. Current active and persistent substance and/or alcohol abuse.
5. Any severe, unstable medical condition (e.g., cardiovascular disorders, diabetes mellitus, respiratory diseases, cancer).
6. Obesity (body mass index > 30).
7. Cognitive dysfunction such as retardation.
8. Known or suspected pregnancy or breastfeeding women.
9. Lactose intolerance or sensitivity.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Oxopurin	Placebo (105 mg Lactose and 510 mg Dextrose)
Pentoxifylline	Oxopurin	Pentoxifylline (Oxopurin 400 mg)

Primary Outcome Measures

Name	Time	Method
Positive and negative symptoms	Subjects will be monitored at baseline and every two weeks for six weeks	Improvement in positive and negative symptoms (Changes in PANSS rates)

Secondary Outcome Measures

Name	Time	Method
Depressive symptoms	Subjects will be monitored at baseline and every two weeks for six weeks	Changes in HAM-D rates

Trial Locations

Locations (1)

Mazor MHC; 🇮🇱 Akko, Israel